(4S)-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-3-hydroxy-2-[6-[4-[4-(3,7,14,18,22-pentahydroxy-2,6,10,15,19,23-hexamethyltetracosan-11-yl)oxybutyl]triazol-1-yl]hexanoylamino]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid | 1450791-23-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4S)-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-3-hydroxy-2-[6-[4-[4-(3,7,14,18,22-pentahydroxy-2,6,10,15,19,23-hexamethyltetracosan-11-yl)oxybutyl]triazol-1-yl]hexanoylamino]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid
• CAS: 1450791-23-7
• 化学式: C₈₈H₁₄₃N₁₇O₁₇
• 分子量: 1711.21
• InChiKey: MWVQSTGUKQDQFU-SUSIORCISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.8
• 重原子数：
  122
• 可旋转键数：
  64
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  554
• 氢给体数：
  19
• 氢受体数：
  21

反应信息

• 作为产物：
  描述：

  、 14-(hex-5-yn-1-yloxy)-2,6,10,15,19,23-hexamethyltetracosane-3,7,11,18,22-pentaol 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 甲醇 为溶剂， 反应 4.0h， 以24%的产率得到(4S)-5-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-1-amino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-(diaminomethylideneamino)-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]amino]-4-[[(2S)-2-[[(2S)-3-hydroxy-2-[6-[4-[4-(3,7,14,18,22-pentahydroxy-2,6,10,15,19,23-hexamethyltetracosan-11-yl)oxybutyl]triazol-1-yl]hexanoylamino]propanoyl]amino]hexanoyl]amino]-5-oxopentanoic acid
  参考文献：
  名称：

  Synthesis and Characterization of Time-resolved Fluorescence Probes for Evaluation of Competitive Binding to Melanocortin Receptors

  摘要：

  Probes for use in time-resolved fluorescence competitive binding assays at melanocortin receptors based on the parental ligands MSH(4), MSH(7), and NDP-alpha-MSH were prepared by solid phase synthesis methods, purified, and characterized. The saturation binding of these probes was studied using HEK-293 cells engineered to overexpress the human melanocortin 4 receptor (hMC4R) as well as the human cholecystokinin 2 receptor (hCCK2R). The ratios of non-specific binding to total binding approached unity at high concentrations for each probe. At low probe concentrations, receptor-mediated binding and uptake was discernable, and so probe concentrations were kept as low as possible in determining K-d values. The Eu-DTPA-PEGO-MSH(4) probe exhibited low specific binding relative to non-specific binding, even at low nanomolar concentrations, and was deemed unsuitable for use in competition binding assays. The Eu-DTPA-PEGO probes based on MSH(7) and NDP-alpha-MSH exhibited K-d values of 27 +/- 3.9 nM and 4.2 +/- 0.48 nM, respectively, for binding with hMC4R. These probes were employed in competitive binding assays to characterize the interactions of hMC4R with monovalent and divalent MSH(4), MSH(7), and NDP-alpha-MSH constructs derived from squalene. Results from assays with both probes reflected only statistical enhancements, suggesting improper ligand spacing on the squalene scaffold for the divalent constructs. The K-i values from competitive binding assays that employed the MSH(7)-based probe were generally lower than the K-i values obtained when the probe based on NDP-alpha-MSH was employed, which is consistent with the greater potency of the latter probe. The probe based on MSH(7) was also competed with monovalent, divalent, and trivalent MSH(4) constructs that previously demonstrated multivalent binding in competitive binding assays against a variant of the probe based on NDP-alpha-MSH. Results from these assays confirm multivalent binding, but suggest a more modest increase in avidity for these MSH(4) constructs than was previously reported. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.052

文献信息

• Synthesis and Characterization of Time-resolved Fluorescence Probes for Evaluation of Competitive Binding to Melanocortin Receptors
  作者：Ramesh Alleti、Josef Vagner、Dilani Chathurika Dehigaspitiya、Valerie E. Moberg、N.G.R.D. Elshan、Narges K. Tafreshi、Nabila Brabez、Craig S. Weber、Ronald M. Lynch、Victor J. Hruby、Robert J. Gillies、David L. Morse、Eugene A. Mash

  DOI：10.1016/j.bmc.2013.06.052

  日期：2013.9

  Probes for use in time-resolved fluorescence competitive binding assays at melanocortin receptors based on the parental ligands MSH(4), MSH(7), and NDP-alpha-MSH were prepared by solid phase synthesis methods, purified, and characterized. The saturation binding of these probes was studied using HEK-293 cells engineered to overexpress the human melanocortin 4 receptor (hMC4R) as well as the human cholecystokinin 2 receptor (hCCK2R). The ratios of non-specific binding to total binding approached unity at high concentrations for each probe. At low probe concentrations, receptor-mediated binding and uptake was discernable, and so probe concentrations were kept as low as possible in determining K-d values. The Eu-DTPA-PEGO-MSH(4) probe exhibited low specific binding relative to non-specific binding, even at low nanomolar concentrations, and was deemed unsuitable for use in competition binding assays. The Eu-DTPA-PEGO probes based on MSH(7) and NDP-alpha-MSH exhibited K-d values of 27 +/- 3.9 nM and 4.2 +/- 0.48 nM, respectively, for binding with hMC4R. These probes were employed in competitive binding assays to characterize the interactions of hMC4R with monovalent and divalent MSH(4), MSH(7), and NDP-alpha-MSH constructs derived from squalene. Results from assays with both probes reflected only statistical enhancements, suggesting improper ligand spacing on the squalene scaffold for the divalent constructs. The K-i values from competitive binding assays that employed the MSH(7)-based probe were generally lower than the K-i values obtained when the probe based on NDP-alpha-MSH was employed, which is consistent with the greater potency of the latter probe. The probe based on MSH(7) was also competed with monovalent, divalent, and trivalent MSH(4) constructs that previously demonstrated multivalent binding in competitive binding assays against a variant of the probe based on NDP-alpha-MSH. Results from these assays confirm multivalent binding, but suggest a more modest increase in avidity for these MSH(4) constructs than was previously reported. (C) 2013 Elsevier Ltd. All rights reserved.